Lolich is best known for his performance in the 1968 World Series, when he allowed just five runs in three complete games, winning all three including the final and decisive game. Mickey also helped himself at the plate in game 2 when he hit the first and only home run of his 16 year career. He remains the last pitcher to win three complete games in a single World Series, and was the last to win three at all until Randy Johnson did that in 2001. Lolich was given the World Series MVP Award for his superb performance.

Lolich was a picture of consistency, winning 14 or more games for ten consecutive seasons, including 25 in 1971 and 22 in 1972. He also struck out 200 or more batters seven times during his career, and ranks third among left-handers (behind Steve Carlton and Randy Johnson) in career strikeouts with 2,832.

After suffering through the 1975 season, in which he lost 18 games, the Tigers traded him to the New York Mets with outfielder Billy Baldwin in exchange for star outfielder Rusty Staub and pitcher Bill Laxton. In 1976, Lolich's slump continued with the Mets, as he won just 8 games while losing 13, leading him to retire. He returned to his home in suburbanDetroit, opened a doughnut shop, and skipped the 1977 season. He eventually re-entered the free agent market, signed a contract with the San Diego Padres, and pitched for them during the 1978 and 1979 seasons before permanently retiring. At the time of his retirement, he held the Major League Baseball record for most career strike-outs by a left-handed pitcher.

Lolich was deemed to be righthanded, but a tricycle accident that occurred while Lolich was young forced him to adapt to using his left hand. This would come to include baseball, once he began to play it. Although he became a lefthanded pitcher, Lolich still writes righthanded.

After Lolich's career ended, he continued to run his doughnut shop in Lake Orion, Michigan (20 minutes South of Lapeer, Michigan) for several years before he sold the business and retiring to his home in Oregon. Today, he is active in charitable work and serves as a coach at the Detroit Tigers' fantasy camp in Lakeland, Florida.

In 2003, Lolich was one of the 26 players selected to the final ballot by the Baseball Hall of Fame's Veterans Committee. He received only 13 votes, placing him far below the 75% required for election. Lolich has often said the fact that he never won the Cy Young Award was a factor in not receiving sufficient votes to be elected to the Hall of Fame.